Synthesizing Pd-based high entropy alloy nanoclusters for enhanced oxygen reduction.

We report the synthesis of uniform Pd-based high-entropy alloy clusters via rapid Joule heating. The quinary PdMnFeCuNi clusters exhibit 4.95 times higher mass activity than the Commercial Pt/C for the oxygen reduction reaction, and outstanding stability with only 2 mV decay in the half-wave potential after 20 000 cycles of testing.

RFEM: A framework for essential microRNA identification in mice based on rotation forest and multiple feature fusion.

With the increasing number of microRNAs (miRNAs), identifying essential miRNAs has become an important task that needs to be solved urgently. However, there are few computational methods for essential miRNA identification. Here, we proposed a novel framework called Rotation Forest for Essential MicroRNA identification (RFEM) to predict the essentiality of miRNAs in mice. We first constructed 1,264 miRNA features of all miRNA samples by fusing 38 miRNA features obtained from the PESM paper and 1,226 miRNA functional features calculated based on miRNA-target gene interactions. Then, we employed 182 training samples with 1,264 features to train the rotation forest model, which was applied to compute the essentiality scores of the candidate samples. The main innovations of RFEM were as follows: 1) miRNA functional features were introduced to enrich the diversity of miRNA features; 2) the rotation forest model used decision tree as the base classifier and could increase the difference among base classifiers through feature transformation to achieve better ensemble results. Experimental results show that RFEM significantly outperformed two previous models with the AUC (AUPR) of 0.942 (0.944) in three comparison experiments under 5-fold cross validation, which proved the model's reliable performance. Moreover, ablation study was further conducted to demonstrate the effectiveness of the novel miRNA functional features. Additionally, in the case studies of assessing the essentiality of unlabeled miRNAs, experimental literature confirmed that 7 of the top 10 predicted miRNAs have crucial biological functions in mice. Therefore, RFEM would be a reliable tool for identifying essential miRNAs.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

The membrane-cytoplasmic linker defines activity of FtsH proteases in Pseudomonas aeruginosa clone C.

Pandemic Pseudomonas aeruginosa clone C strains encode two inner-membrane associated ATP-dependent FtsH proteases. PaftsH1 is located on the core genome and supports cell growth and intrinsic antibiotic resistance, whereas PaftsH2, a xenolog acquired through horizontal gene transfer from a distantly related species, is unable to functionally replace PaftsH1. We show that purified PaFtsH2 degrades fewer substrates than PaFtsH1. Replacing the 31-amino acid-extended linker region of PaFtsH2 spanning from the C-terminal end of the transmembrane helix-2 to the first seven highly divergent residues of the cytosolic AAA+ ATPase module with the corresponding region of PaFtsH1 improves hybrid-enzyme substrate processing in vitro and enables PaFtsH2 to substitute for PaFtsH1 in vivo. Electron microscopy indicates that the identity of this linker sequence influences FtsH flexibility. We find membrane-cytoplasmic (MC) linker regions of PaFtsH1 characteristically glycine-rich compared to those from FtsH2. Consequently, introducing three glycines into the membrane-proximal end of PaFtsH2's MC linker is sufficient to elevate its activity in vitro and in vivo. Our findings establish that the efficiency of substrate processing by the two PaFtsH isoforms depends on MC linker identity and suggest that greater linker flexibility and/or length allows FtsH to degrade a wider spectrum of substrates. As PaFtsH2 homologs occur across bacterial phyla, we hypothesize that FtsH2 is a latent enzyme but may recognize specific substrates or is activated in specific contexts or biological niches. The identity of such linkers might thus play a more determinative role in the functionality of and physiological impact by FtsH proteases than previously thought.

A universal strategy for green and surfactant-free synthesis of noble metal nanoparticles.

We propose a universal, green, and surfactant-free strategy to synthesize noble metal particles with high monodispersity using gaseous H2 as a reducing agent in a solution at 60 °C. The prepared Pt nanoparticles have a 24 mV more positive half-wave potential than the commercially available Pt/C in the oxygen reduction reaction, while showing high durability with negligible half-wave potential decay after 10 000 cycles of testing.

Clinical practice and outcomes of preimplantation genetic testing for CMT1A using a novel direct detection method.

Background: Charcot-Marie-Tooth type 1A (CMT1A), the most frequent type of Charcot-Marie-Tooth disease, is mainly caused by a 1.4-Mb duplication containing the PMP22 gene. There is no effective treatment other than general supportive care and symptomatic treatment. Preimplantation genetic testing for monogenic defects (PGT-M) is an alternative approach for obtaining healthy babies. Methods: A new technology and analysis method based on next-generation sequencing (NGS) was developed to detect duplication mutations directly. Simultaneously, aneuploidy and linkage analyses were performed to achieve a comprehensive and accurate embryo diagnosis. Results: Eight couples were recruited in this study; PMP22 duplication was validated in seven couples, and PMP22 splicing mutation was found in one. Forty-five embryos from 12 PGT cycles were successfully detected using this novel method. The direct detection results for all embryos were consistent with the linkage analyses, suggesting a 100 % accuracy rate, and the aneuploidy rate of the biopsied blastocysts was 33.3 %. Eventually, 18 of the 45 diagnosed embryos were deemed suitable for transfer. Four healthy babies from three families were delivered and their genetic status confirmed by amniocentesis. Additionally, there were no adverse effects of anesthesia or increased pregnancy complications during PGT-M in female patients with CMT1A. Conclusions: This study provided a simple, reliable, and efficient method that can directly detect PMP22 mutations based on NGS data and does not require positive family members. A clinical workflow for CMT1A interruption in the offspring before embryo implantation is also summarized.

Multiple Roads to Success: A Latent Class Analysis on Successful Ageing Among Hong Kong Near-Centenarians and Centenarians (NCC).

Notwithstanding the oldest-old cohort being the fastest-growing population in most ageing societies, characterizing successful ageing in adults of advanced age, such as nonagenarians and centenarians, remains challenging. This study investigated the successful ageing subphenotypes using the data from Hong Kong Centenarian Study 2. Between April 2021 and September 2022, 146 family caregivers of community-dwelling older adults aged 95 or above were interviewed by phone. Latent class analysis identified three classes-Overall Frail (46.6%) with poor mobility, cognitive and functional health, Nonambulant (37.0%) but good functional health, and Robust (16.4%) with overall good health-from 11 indicators based on caregivers' reports. Although we found a low prevalence of fulfillment of all indicators of successful ageing, our findings will help care professionals appreciate the heterogeneity underlying partial successful ageing in this vulnerable cohort for segmented and targeted healthy longevity interventions.

Sequential embryo transfer versus double cleavage-stage embryo or double blastocyst transfer in patients with recurrent implantation failure with frozen-thawed embryo transfer cycles: a cohort study.

Background: Recurrent implantation failure (RIF) is more common among patients receiving assisted reproductive treatment. Many efforts have been made to increase the incidence of clinical pregnancy among patients with RIF. The effect of the sequential transfer procedure, a two-step interval transfer of a cleavage-stage embryo followed by a blastocyst in one transfer cycle, on the clinical outcomes of RIF patients remains controversial. Methods: In total, 1774 frozen-thawed embryo transfer (FET) cycles in RIF patients were included. Of these cycles, 302 were sequential embryo transfer (ET) cycles, 979 were double day 3 cleavage-stage ET cycles, and 493 were double blastocyst ET cycles. The primary outcomes were the rates of implantation, clinical pregnancy and multiple pregnancy, and the secondary outcomes were the rates of hCG positive, early miscarriage and ectopic pregnancy. Results: The implantation, hCG positive, and clinical pregnancy rates in the sequential ET group (32.1%, 58.9%, 50.7%) were significantly higher than those in the day 3 cleavage-stage ET group (24.9%, 46.5%, 40.4%) and were similar to those in the blastocyst transfer group (30.1%, 56.4%, 47.1%). The early miscarriage rate in the blastocyst transfer group was significantly higher than that in the cleavage-stage ET group (17.2% vs. 8.1%, P <0.05), while the ectopic pregnancy rate in the blastocyst transfer group was significantly lower than that in the cleavage-stage ET group (0.4% vs. 3.0%, P <0.05). The multiple pregnancy rate in the sequential ET group was significantly lower than that in the cleavage-stage ET group (17.0% vs. 25.5%, P <0.05) and the blastocyst transfer group (17.0% vs. 27.6%, P <0.05). When cycles of blastocyst culture failure were excluded, the clinical pregnancy rate was significantly higher (55.7% vs. 47.1%, P <0.05), and the early miscarriage rate and multiple pregnancy rate were significantly lower (8.5% vs. 17.2%, 17.7% vs. 27.6%; P <0.05, respectively) in the sequential ET group than in the double blastocyst ET group. Conclusions: Sequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF.

Selective edge etching of Pd metallene for enhanced formic acid electrooxidation.

We develop a facile, selective edge etching strategy to create edge sites in Pd metallene using acetic acid. The created edge sites remarkably increase the electrochemically active surface area but reduce the charge transfer resistance, resulting in significant enhancement of catalytic activity and stability toward formic acid oxidation.

Impact of thyroid-stimulating hormone levels after controlled ovarian hyperstimulation on in vitro fertilization/intracytoplasmic sperm injection outcomes in women with fresh embryo transfer: a prospective cohort study.

Objective: Maternal hypothyroidism before and during pregnancy is associated with an increased risk of adverse pregnancy outcomes; many studies have evidenced that controlled ovarian hyperstimulation (COH) triggers a significant increase in the levels of TSH; however, no large-scale prospective studies have evaluated the impact of TSH levels after COH on assisted reproductive technology outcomes. The aim of this prospective study was to investigate whether in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes are affected by TSH levels after COH in women with fresh embryo transfer (ET). Methods: A total of 664 patients who underwent IVF/ICSI treatment and received fresh ET at the Peking University Third Hospital were included in this study. The rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were analyzed. Results: The patients were categorized into two groups based on serum TSH levels after COH (0.55 mIU/L < TSH < 2.5 mIU/L: n= 449, 2.5 mIU/L ≤ TSH ≤ 4.78 mIU/L: n= 215). There were no significant differences in the rates of clinical pregnancy, miscarriage, and live birth between the two groups, even after adjusting for age, body mass index (BMI), thyroid antibody positivity, and COH protocols. However, the preterm delivery rate was significantly higher in women with TSH < 2.5 mIU/L than in those with TSH ≥ 2.5 mIU/L, even after adjusting for relevant confounding factors. There was no significant difference in live birth weight between the two groups. Discussion: Mildly elevated TSH levels (TSH ≥ 2.5 mIU/L) after COH did not affect IVF/ICSI outcomes, and strict control of TSH levels within 2.5 mIU/L after COH might not be necessary. Additionally, strictly controlled TSH levels (TSH < 2.5 mIU/L) may increase preterm delivery risk.

Tensile-Strained Holey Pd Metallene toward Efficient and Stable Electrocatalysis.

Noble metal-based metallenes are attracting intensive attention in energy catalysis, but it is still very challenging to precisely control the surface structures of metallenes for higher catalytic properties on account of their intrinsic thermodynamic instability. Herein, the synthesis of tensile-strained holey Pd metallene by oxidative etching is reported using hydrogen peroxide, which exhibits highly enhanced catalytic activity and stability in comparison with normal Pd metallene toward both oxygen reduction reaction and formic acid oxidation. The pre-prepared Pd metallene functions as a catalyst to decompose hydrogen peroxide, and the Pd atoms in amorphous regions of Pd metallene are preferentially removed by the introduced hydrogen peroxide during the etching process. The greatly enhanced ORR activity is mainly determined by the strong electrostatic repulsion between intermediate O* and the dopant O, which balances the adsorption strength of O* on Pd sites, ultimately endowing a weakened adsorption energy of O* on TH-Pd metallene. This work creates a facile and economical strategy to precisely shape metallene-based nanoarchitectures with broad applications for energy systems and sensing devices.

Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history.

Hereditary tumor syndromes have garnered substantial attention due to their adverse effects on both the physical and psychological health of patients, as well as the elevated risk of transmission to subsequent generations. This has prompted a growing interest in exploring preimplantation genetic testing (PGT) as a treatment option to mitigate and eliminate these impacts. Several studies have demonstrated that de novo variants have become a great cause of many hereditary tumor syndromes, which introduce certain difficulties to PGT. In the absence of adequate genetic linkage information (parents and offspring), haplotype construction seems unrealizable. In the study, researchers used single sperm or affected embryos as proband to perform single-nucleotide polymorphism linkage analysis for cases with de novo variants. For complicated variants, the strategy that sperm combined with embryo detection will increase accuracy while avoiding the limitations and potential failures of using a single detection material. The study recruited 11 couples with male de novo carriers, including 3 tumor types and 4 genes. To date, 4 couples have been clinically confirmed as pregnant and three healthy babies have been born. The results of amniocentesis or umbilical cord blood verification were consistent with the results of PGT-M. The study aims to introduce the application of the PGT-M strategy in hereditary tumor syndromes.

Evolution of cyclic di-GMP signalling on a short and long term time scale.

Diversifying radiation of domain families within specific lineages of life indicates the importance of their functionality for the organisms. The foundation for the diversifying radiation of the cyclic di-GMP signalling network that occurred within the bacterial kingdom is most likely based in the outmost adaptability, flexibility and plasticity of the system. Integrative sensing of multiple diverse extra- and intracellular signals is made possible by the N-terminal sensory domains of the modular cyclic di-GMP turnover proteins, mutations in the protein scaffolds and subsequent signal reception by diverse receptors, which eventually rewires opposite host-associated as well as environmental life styles including parallel regulated target outputs. Natural, laboratory and microcosm derived microbial variants often with an altered multicellular biofilm behaviour as reading output demonstrated single amino acid substitutions to substantially alter catalytic activity including substrate specificity. Truncations and domain swapping of cyclic di-GMP signalling genes and horizontal gene transfer suggest rewiring of the network. Presence of cyclic di-GMP signalling genes on horizontally transferable elements in particular observed in extreme acidophilic bacteria indicates that cyclic di-GMP signalling and biofilm components are under selective pressure in these types of environments. On a short and long term evolutionary scale, within a species and in families within bacterial orders, respectively, the cyclic di-GMP signalling network can also rapidly disappear. To investigate variability of the cyclic di-GMP signalling system on various levels will give clues about evolutionary forces and discover novel physiological and metabolic pathways affected by this intriguing second messenger signalling system.

Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis.

Background: Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies. Methods: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023. To pool data, fixed-effects or random-effects models were used where appropriate. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Results: A total of 13 studies (4 cohort studies and 9 case-control studies) were included in the analysis, with a total of 625,738 participants. The highest UPFs consumption was associated with increased risk of colorectal cancer (OR = 1.23, 95% CI: 1.10-1.38), colon cancer (OR = 1.25, 95% CI: 1.14-1.36), and breast cancer (OR = 1.10, 95% CI: 1.00-1.20) but not rectal cancer (OR = 1.18, 95% CI: 0.97-1.43) and prostate cancer (OR = 1.03, 95% CI: 0.93-1.12). In addition, the subgroup analyses showed that a positive association between UPFs consumption and colorectal cancer was observed among men (OR = 1.31, 95% CI: 1.15-1.50), whereas no significant association was observed among women (OR = 1.10, 95% CI: 0.94-1.29). Conclusion: The present meta-analysis suggests that high UPFs consumption is associated with a significantly increased risk of certain site-specific cancers, especially the digestive tract and some hormone-related cancers. However, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Downregulation of a CT10 regulator of kinase (Crk) promotes the formation of diapause embryos in the brine shrimp Artemia.

To survive under harsh environments, embryonic development of Artemia was arrested at the gastrula stage and released as the diapause embryo. Cell cycle and metabolism were highly suppressed in this state of quiescence. However, cellular mechanisms underlying diapause remain largely unclear. In this study, we found that the expression level of a CT10 regulator of kinase-encoding gene (Ar-Crk) in diapause embryos was significantly lower than non-diapause embryos at the early embryogenetic stage of Artemia. Knockdown of Ar-Crk by RNA interference induced formation of diapause embryos, while the control group produced nauplii. Western blot analysis and metabolic assays revealed that the diapause embryos produced by Ar-Crk-knocked-down Artemia had similar characteristics of diapause markers, arrested cell cycle, and suppressed metabolism with those diapause embryos produced by natural oviparous Artemia. Transcriptomic analysis of Artemia embryos revealed knockdown of Ar-Crk induced downregulation of the aurora kinase A (AURKA) signaling pathway, as well as energetic and biomolecular metabolisms. Taken together, we proposed that Ar-Crk is a crucial factor in determining the process of diapause in Artemia. Our results provide insight into the functions of Crk in fundamental regulations such as cellular quiescence.

A cytological revisit on parthenogenetic Artemia and the deficiency of a meiosis-specific recombinase DMC1 in the possible transition from bisexuality to parthenogenesis.

Although parthenogenesis is widespread in nature and known to have close relationships with bisexuality, the transitional mechanism is poorly understood. Artemia is an ideal model to address this issue because bisexuality and "contagious" obligate parthenogenesis independently exist in its congeneric members. In the present study, we first performed chromosome spreading and immunofluorescence to compare meiotic processes of Artemia adopting two distinct reproductive ways. The results showed that, unlike conventional meiosis in bisexual Artemia, meiosis II in parthenogenic Artemia is entirely absent and anaphase I is followed by a single mitosis-like equational division. Interspecific comparative transcriptomics showed that two central molecules in homologous recombination (HR), Dmc1 and Rad51, exhibited significantly higher expression in bisexual versus parthenogenetic Artemia. qRT-PCR indicated that the expression of both genes peaked at the early oogenesis and gradually decreased afterward. Knocking-down by RNAi of Dmc1 in unfertilized females of bisexual Artemia resulted in a severe deficiency of homologous chromosome pairing and produced univalents at the middle oogenesis stage, which was similar to that of parthenogenic Artemia, while in contrast, silencing Rad51 led to no significant chromosome morphological change. Our results indicated that Dmc1 is vital for HR in bisexual Artemia, and the deficiency of Dmc1 may be correlated with or even possibly one of core factors in the transition from bisexuality to parthenogenesis.

Regulation of biofilm formation in Zymomonas mobilis to enhance stress tolerance by heterologous expression of pfs and luxS.

Zymomonas mobilis is a potential alternative of Saccharomyces cerevisiae to produce cellulosic ethanol with strengths in cofactor balance, but its lower tolerance to inhibitors in the lignocellulosic hydrolysate restricts the application. Although biofilm can improve bacteria stress tolerance, regulating biofilm formation in Z. mobilis is still a challenge. In this work, we constructed a pathway by heterologous expressing pfs and luxS from Escherichia coli in Z. mobilis to produce AI-2 (autoinducer 2), a universal quorum-sensing signal molecule, to control cell morphology for enhancing stress tolerance. Unexpectedly, the results suggested that neither endogenous AI-2 nor exogenous AI-2 promoted biofilm formation, while heterologous expression of pfs can significantly raise biofilm. Therefore, we proposed that the main factor in assisting biofilm formation was the product accumulated due to heterologous expression of pfs, like methylated DNA. Consequently, ZM4::pfs produced more biofilm, which presented an enhanced tolerance to acetic acid. All these findings provide a novel strategy to improve the stress tolerance of Z. mobilis by enhancing biofilm formation for efficient production of lignocellulosic ethanol and other value-added chemical products.

Identification and characterization of the Doublesex gene and its mRNA isoforms in the brine shrimp Artemia franciscana.

Doublesex (DSX) proteins are members of the Doublesex/mab-3-related (DMRT) protein family and play crucial roles in sex determination and differentiation among the animal kingdom. In the present study, we identified two Doublesex (Dsx)-like mRNA isoforms in the brine shrimp Artemia franciscana (Kellogg 1906), which are generated by the combination of alternative promoters, alternative splicing and alternative polyadenylation. The two transcripts exhibited sex-biased enrichment, which we termed AfrDsxM and AfrDsxF. They share a common region which encodes an identical N-terminal DNA-binding (DM) domain. RT-qPCR analyses showed that AfrDsxM is dominantly expressed in male Artemia while AfrDsxF is specifically expressed in females. Expression levels of both isoforms increased along with the developmental stages of their respective sexes. RNA interference with dsRNA showed that the knockdown of AfrDsxM in male larvae led to the appearance of female traits including an ovary-like structure in the original male reproductive system and an elevated expression of vitellogenin. However, silencing of AfrDsxF induced no clear phenotypic change in female Artemia. These results indicated that the male AfrDSXM may act as inhibiting regulator upon the default female developmental mode in Artemia. Furthermore, electrophoretic mobility shift assay analyses revealed that the unique DM domain of AfrDSXs can specifically bind to promoter segments of potential downstream target genes like AfrVtg. These data show that AfrDSXs play crucial roles in regulating sexual development in Artemia, and further provide insight into the evolution of sex determination/differentiation in sexual organisms.

Efficacy and safety of remimazolam-based sedation for intensive care unit patients undergoing upper gastrointestinal endoscopy: a cohort study.

BACKGROUND: Remimazolam is a novel ultra-short-acting sedative, but its safety and adverse events (AEs) in high-risk patients in the intensive care unit (ICU) setting remain unknown. METHODS: This was a single-center, retrospective study that compared remimazolam to propofol and midazolam in patients undergoing upper gastrointestinal endoscopy. The primary outcome was the incidence of treatment-related AEs. The secondary outcomes were the time to extubation, the length of ICU stay, and the average cost of sedative per case. RESULTS: Of the 88 patients analyzed, 47 were treated with remimazolam (mean dose, 7.90±4.84 mg), and 41 were treated with propofol (21.19±17.98 mg) or midazolam (3.08±2.17 mg). There was no statistically significant difference in the average duration of the endoscopic procedure (35.89±13.37 min vs. 44.51±21.68 min, P=0.133) or the time to extubation (15.00±9.75 h vs. 20.59±18.71 h, P=0.211) in the remimazolam group (group I) compared to the propofol or midazolam group (group II). ICU stays (5.40±2.93 d vs. 4.63±3.31 d, P=0.072) and treatment-related AEs (48.61% vs. 51.38%, P=0.056) were similar between groups. The average cost of sedative per case was significantly lower in the group I than in the group II (RMB 16.07±10.58 yuan vs. RMB 24.37±15.46 yuan, P=0.016). CONCLUSION: Remimazolam-based sedation was noninferior to the classic sedatives and had lower average cost per case, indicating that it may be used as a promising sedative for high-risk patients during endoscopic procedures in the ICU setting.